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Biomedical subjects

R Gomez

Publications and source records attributed to R Gomez.

At least 91 records · Page 5Linked to original sources

A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition.

OBJECTIVE: There is no evidence for the participation of the human fetus in the mechanisms responsible for the onset of preterm labor. We propose that preterm labor in the setting of infection results from the actions of proinflammatory cytokines secreted as part of the fetal and/or maternal host response to microbial invasion. The objective of this study was to determine whether a systemic fetal inflammatory response, defined as an elevation of fetal plasma interleukin-6 concentrations, has a temporal relationship with the commencement of labor. STUDY DESIGN: After informed consent was obtained, amniocentesis and cordocentesis were performed in 41 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for both aerobic and anaerobic bacteria, as well as for mycoplasmas. Fetal plasma interleukin-6 was assayed by a sensitive and specific immunoassay. Statistical analyses included contingency tables and survival analysis with time-dependent Cox regression hazard modeling. RESULTS: Microbial invasion of the amniotic cavity was present in 58.5% (24/41) of patients. Fetuses with fetal plasma interleukin-6 concentrations > 11 pg/mL had a higher rate of spontaneous preterm delivery within 48 and 72 hours of the procedure than those with fetal plasma interleukin-6 levels < or = 11 pg/mL (88% vs 29% and 88% vs 35%, respectively; P < .05 for all comparisons). Moreover, patients with initiation of labor and delivery within 48 hours of the procedure had a higher proportion of fetuses with plasma interleukin-6 values > 11 pg/mL than patients delivered > 48 hours (58% [7/12] vs 8% [1/13], respectively; P < .05). Survival analysis indicated that fetuses with elevated fetal plasma interleukin-6 levels had a shorter cordocentesis-to-delivery interval than those without elevated fetal plasma interleukin-6 concentrations (median 0.8 days [range 0.1 to 5] vs median 6 days [range 0.2 to 33.6], respectively; P < .05). Time-dependent Cox regression hazard modeling indicated that fetal plasma interleukin-6 level was the only covariate significantly associated with the duration of pregnancy after we adjusted for gestational age, amniotic fluid interleukin-6 level, and the microbiologic state of the amniotic cavity (P < .01). CONCLUSION: A systemic fetal proinflammatory cytokine response is followed by the onset of spontaneous preterm parturition in patients with preterm premature rupture of membranes.

Acute-Phase Reaction↗

The fetal inflammatory response syndrome.

OBJECTIVE: The objective of this study was to determine the frequency and clinical significance of a systemic inflammatory response as defined by an elevated plasma interleukin-6 concentration in fetuses with preterm labor or preterm premature rupture of membranes. STUDY DESIGN: Amniocenteses and cordocenteses were performed in 157 patients with preterm labor and preterm premature rupture of membranes. Written informed consent and multi-institutional review board approvals were obtained. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid and fetal plasma interleukin-6 concentrations were measured with a sensitive and specific immunoassay. Statistical analyses included contingency tables, receiver operating characteristic curve analysis, and multiple logistic regression. RESULTS: One hundred five patients with preterm labor and 52 patients with preterm premature rupture of membranes were included in this study. The overall prevalence of severe neonatal morbidity (defined as the presence of respiratory distress syndrome, suspected or proved neonatal sepsis, pneumonia, bronchopulmonary dysplasia. intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis) among survivors was 34.8% (54/155). Neonates in whom severe neonatal morbidity developed had higher concentrations of fetal plasma interleukin-6 than fetuses without development of severe neonatal morbidity (median 14.0 pg/mL, range 0.5 to 900 vs median 5.2 pg/mL, range 0.3 to 900, respectively; P < .005). Multivariate analysis was performed to explore the relationship between the presence of a systemic fetal inflammatory response and subsequent neonatal outcome. To preserve a meaningful temporal relationship between the results of fetal plasma interleukin-6 concentrations and the occurrence of severe neonatal morbidity, the analysis was restricted to 73 fetuses delivered within 7 days of cordocentesis who survived. The prevalence of severe neonatal morbidity in this subset of patients was 53.4% (39/73). A fetal plasma interleukin-6 cutoff value of 11 pg/mL was used to define the presence of a systemic inflammatory response. The prevalence of a fetal plasma interleukin-6 level > 11 pg/mL was 49.3% (36/73). Fetuses with fetal plasma interleukin-6 concentrations > 11 pg/mL had a higher rate of severe neonatal morbidity than did those with fetal plasma interleukin-6 levels < or = 11 pg/mL (77.8% [28/36] vs 29.7% [11/37], respectively; P < .001). Stepwise logistic regression analysis demonstrated that the fetal plasma interleukin-6 concentration was an independent predictor of the occurrence of severe neonatal morbidity (odds ratio 4.3, 95% confidence interval 1 to 18.5) when adjusted for gestational age at delivery, the cause of preterm delivery (preterm labor or preterm premature rupture of membranes), clinical chorioamnionitis, the cordocentesis-to-delivery interval, amniotic fluid culture, and amniotic fluid interleukin-6 results. CONCLUSION: A systemic fetal inflammatory response, as determined by an elevated fetal plasma interleukin-6 value, is an independent risk factor for the occurrence of severe neonatal morbidity.

Acute-Phase Reaction↗

The clinical significance of antenatal detection of discordant umbilical arteries.

OBJECTIVE: To evaluate the clinical significance of the antenatally detected discordant umbilical arteries (UAs). METHODS: Women with singleton gestations undergoing sonographic evaluations were examined for the presence of discordant UAs. Transverse and longitudinal diameters as well as the area of both UAs were measured. Doppler flow velocity waveforms were recorded from both arteries. Macroscopic and microscopic examination of the umbilical cord was performed after delivery and the area of each artery was measured. Mann-Whitney U test and Spearman rank correlation were used for statistical purposes. RESULTS: Data are presented as median (range). Discordance between UAs was found in 14 of 1012 women who underwent sonographic examinations. The vessel diameters and areas differed significantly between the discordant UAs (diameter 2.9 [1-4.3] versus 4.5 [3.8-6.5] mm, P < .001; area 6.6 [0.78-14.5] versus 16.25 [11.33-33.16] mm2, P < .001). A significant difference between UA size was confirmed after delivery (area 1.68 [0.9-3.06] versus 4.17 [1.12-13.8] mm2, P < .005). The difference in the area of the UAs in utero and at microscopic examination correlated significantly (r = .94, P < .05). In all cases, the resistance index was higher in the smaller artery than in the larger artery (0.71 [0.59-0.8] versus 0.6 [0.48-0.75] P < .01). Abnormal insertion of the umbilical cord or an abnormality of the placenta was present in eight cases. Perinatal death occurred only in a trisomic infant born at 24 weeks' gestation. CONCLUSION: The clinical significance of discordant UAs is that newborns are generally in good condition at birth and placental anomalies are common in this group of parturients. Abnormal Doppler velocimetry of the smaller UA should be taken with caution, because it does not seem to be associated with poor perinatal outcome.

Adult↗

Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates subsequently develop bronchopulmonary dysplasia.

OBJECTIVE: To determine if an intrauterine sub-clinical inflammatory process is a risk factor for the development of bronchopulmonary dysplasia. METHODS: A cohort study was conducted in patients who met the following criteria: (1) Singleton gestation; (2) preterm labor or preterm premature rupture of the membranes; (3) amniocentesis for microbiologic studies of the amniotic fluid and (4) delivery between 24 and 28 weeks of gestation. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen for 28 days or longer after birth, associated with compatible chest radiographic findings. Amniotic fluid interleukin-8, was measured using a specific immunoassay. Logistic regression analysis and bootstrap procedure were used for statistical purposes. RESULTS: Forty-seven patients met the inclusion criteria for this study. Among these patients, the prevalence of bronchopulmonary dysplasia was 23.4% (11/47). Amniotic fluid culture was positive in 21 out of 47 (44.7%) patients. Median (range) amniotic fluid interleukin-8 concentration was higher in patients whose neonates subsequently developed bronchopulmonary dysplasia than in those who did not (17 [9.8-583.7] ng ml(-1) versus 9.6 [0.91-744] ng ml(-1), P=0.057). An amniotic fluid IL-8 level greater than 11.5 ng ml(-1) was far more common in mothers whose fetuses went on to develop bronchopulmonary dysplasia than in those who did not (10/11 [90.9%] versus 17/36 [47%]; P=0.01). This relationship remained significant even after correcting for the effect of gestational age and birthweight (Odds ratio: 11.9; P<0.05). CONCLUSION: Sub-clinical intrauterine inflammation is a risk factor for the subsequent development of bronchopulmonary dysplasia. We propose that in utero aspiration of fluid with high concentration of pro-inflammatory mediators may contribute to the lung injury responsible for the development of bronchopulmonary dysplasia.

Amniotic Fluid↗

Indices of respiratory muscle endurance in healthy subjects.

BACKGROUND: The evaluation of respiratory muscle performance can be described in terms of strength and endurance, the latter usually being measured by means of resistive or threshold inspiratory loads, using devices that are also used for respiratory muscle training. Few authors, however, have published endurance reference values for healthy subjects. To that end, we studied two indices of respiratory muscle endurance in a population of 99 healthy volunteers (50 men, 49 women) divided into five age groups (20-70 years old) applying a modification of the methods of Martyn et al. and Nickerson and Keens. Inspiratory muscle endurance (Tlim) was defined as the time the subject was able to sustain breathing against an inspiratory pressure load equivalent to 80% of the maximum tolerated load (Cmax). Cmax was calculated using a 2-min incremental threshold load. RESULTS: We found that the heaviest inspiratory threshold load tolerated for 2 min and the time a load equivalent to 80% of Cmax (Tlim) could be sustained were not significantly different for male and female subjects. Tlim correlated with Cmax, age, height, and maximum respiratory pressures.

Adult↗

The sperm nuclear basic proteins (SNBPs) of the sponge Neofibularia nolitangere: implications for the molecular evolution of SNBPs.

We have isolated and characterized for the first time, the SNBPs from an organism (Neofibularia nolitangere) of the phylum Porifera (Sponges). We have shown that these proteins consist of histones which, as expected, exhibit an amino acid composition very similar to that of other eukaryotic histones. The finding of histones in the sperm of these primitive organisms provides support to the notion that histones (SNBPs of the histone, H, type) were the proteins present at the onset of SNBP evolution. In contrast, a discrete number of alternative SNBP types (protamine-like, PL; protamine, P, types) seem to have appeared later on in the course of evolution and are found in both protostomes and deuterostomes, most likely as a result of processes of parallel evolution.

Amino Acids↗

Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy.

OBJECTIVE: Ultrasonographically detectable neonatal brain white matter lesions are the most important identifiable risk factor for cerebral palsy. Inflammatory cytokines released during the course of intrauterine infections have been implicated in the genesis of brain white matter lesions and subsequent cerebral palsy. This study was undertaken to determine whether fetuses who subsequently were diagnosed to have periventricular brain white matter lesions could be identified by determining the concentrations of inflammatory cytokines in the amniotic fluid. STUDY DESIGN: Women with complicated preterm gestations underwent amniocentesis for clinical indications. Amniotic fluid concentrations of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and the natural interleukin-1 receptor antagonist were determined by immunoassay. Periventricular white matter lesions of the neonate were diagnosed by neurosonography. Univariate and multivariate analyses were conducted. RESULTS: Ninety-four women and their neonates were included in the study; white matter lesions were diagnosed in 24% (23/94) of the newborns. The mothers of newborns with brain white matter lesions had higher median concentrations of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 (but not interleukin-1 receptor antagonist) in amniotic fluid than did those who were delivered of newborns without white matter lesions (p < 0.01 for each). Acute histologic chorioaminionitis was more common in the placentas of neonate with white matter lesions than in those without these lesions (82% [18/22] vs 42% [30/71], p < 0.005). Neonates with white matter lesions were delivered at a lower mean gestational age and birth weight and had a higher rate of significant complications (including respiratory distress syndrome, intraventricular hemorrhage, and infection-related complications) than did those without white matter lesions. The differences in median interleukin-1beta and interleukin-6 levels between these two groups remained significant after adjustment for gestational age and birth weight (interleukin-6: odds ratio 5.7, 95% confidence interval 1.3 to 24.4; interleukin-1beta: odds ratio 4.4, 95% confidence interval 1.1 to 17.0). Of the 94 newborns included in this study, 11 died before age 6 months and eight had cerebral palsy; all eight had white matter lesions and elevated cytokine levels in amniotic fluid. Histologic chorioamnionitis was more common in the placentas of neonates with cerebral palsy than in those without cerebral palsy (86% [6/7] vs 44% [33/75], p < 0.05). CONCLUSIONS: Infants at risk for development of brain white matter lesions can be identified by the concentrations of interleukin-6 and interleukin-1beta in amniotic fluid. Our findings support the hypothesis that inflammatory cytokines released during the course of intrauterine infection play a role in the genesis of brain white matter lesions.

Amniocentesis↗

Detection of human defensin 5 in reproductive tissues.

OBJECTIVES: This study was undertaken to determine whether tissue-specific defensins are expressed within female reproductive tissues. STUDY DESIGN: Messenger ribonucleic acid from amnion, chorion, endometrium, endocervix, myometrium, placenta, small intestine, peripheral blood lymphocytes, and cervical, endometrial, and trophoblast cell lines was reverse transcribed with a 3'-RACE adapter. 3'-RACE polymerase chain reaction was conducted with an upstream human defensin 5 primer and 3'-RACE adapter primer. Polymerase chain reaction products hybridizing to a human defensin 5 probe were cloned for sequence analysis. Sequence data were compared against a nucleotide sequence database, and secondary structure predictions were made. RESULTS: Chorionic tissue, endocervical tissue, endometrial tissue, and an endometrial cell line all demonstrated a single hybridizing 362 bp polymerase chain reaction product. Sequence analysis of all clones demonstrated near-perfect identity with human defensin 5. CONCLUSIONS: Human endocervix, endometrium, and chorion express defensin 5 at the level of transcription. These findings suggest that a previously unrecognized mechanism of protecting female reproductive tissues against infection, by means of a natural antimicrobial system (defensins), may be present.

Amnion↗

Duration of pregnancy after carbon dioxide laser conization of the cervix: influence of cone height.

OBJECTIVE: To determine if carbon dioxide laser conization of the cervix is a risk factor for preterm delivery in subsequent gestations and to evaluate whether there is any relationship between cone height and duration of pregnancy. METHODS: Patients of fertile age who had carbon dioxide laser conization were followed for reproductive events. Cases were matched one-to-one with controls for known risk factors for preterm delivery. Pregnancy duration, rate of preterm birth, and mode of delivery were studied. Parametric and nonparametric tests were used for statistical analysis. Logistic regression analysis and Cox proportional hazard modeling were used to investigate the relationship between cone height and subsequent preterm delivery. RESULTS: Sixty-four women with singleton pregnancies after carbon dioxide laser conization and 64 controls were included in the study. Overall, no difference was found in the rate of preterm delivery and duration of pregnancy. However, women with cone height of at least 10 mm had a higher rate of preterm delivery than either those with cone height less than 10 mm (five of 23 versus one of 41, P = .01) or the controls (five of 23 versus three of 64, P < .05). Cone height of at least 10 mm remained significant in predicting the occurrence of preterm delivery and the duration of pregnancy after adjusting for known risk factors (odds ratio 11.1, P < .05). CONCLUSION: Cone height of at least 10 mm is an independent risk factor for the duration of pregnancy and for the occurrence of preterm delivery in the subsequent gestation.

Adult↗

Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intraamniotic infection.

We have proposed a model in which the initiation of human parturition in the presence of infection is controlled by the host. Systemic maternal infections such as pyelonephritis or localized infections such as deciduitis can trigger parturition by the activation of the monocyte and macrophage system in peripheral blood and human decidua. Preterm labor and preterm PROM can, according to this, be considered events that occur when the intrauterine or maternal environment is hostile and threaten the survival of the fetal-maternal pair. From this point of view, the initiation of preterm labor may have survival value. Why does intrauterine infection result in preterm labor in some cases and PROM in others? It is possible that regulation of different components of the host response has an important role to play in determining clinical presentation. Thus, if preferential activation of the host response leads to the secretion of uterotonic agents (i.e., prostaglandins), preterm labor will result. On the other hand, if the activation of the host response results predominantly in the production of proteases (i.e., leukocyte elastase and MMPs), patients are more likely to experience PROM. Preterm labor and preterm PROM can be considered expressions of the same basic phenomenon: activation of the host-defense macrophage system. Although we have provided evidence that infection is an important factor in the pathogenesis of these conditions, preterm parturition should be considered as a syndrome with multiple causes.

Amnion↗

Detection of human defensins in the placenta.

PROBLEM: The placenta is a highly selective barrier against the hematogenous dissemination of infectious agents. Despite the presence of seemingly intact physical and immunologic barriers, infections nonetheless occur. These observations prompted the examination of placental tissue, amnion, and chorion for previously unrecognized protective mechanisms. METHOD OF STUDY: Messenger RNA from term placenta, amnion, and chorion were reverse transcribed using a 3' RACE adapter. 3' rapid amplification of cDNA ends (RACE)-polymerase chain reaction (PCR) was conducted on cDNA from these tissues to detect the presence of human defensins. Southern analysis and partial sequence analysis were subsequently performed to confirm identity. RESULTS: PCR amplification of placental, amnion, and chorion cDNA yielded a 468-bp product and a weakly detectable band of 300 bp. Southern analysis demonstrated two corresponding hybridizing bands in the placenta, amnion, and chorion but not from a negative cDNA control. Partial sequence analysis of the 468-bp product from placenta confirmed the presence of either defensin 1 or 3 in human placenta. CONCLUSIONS: The human placenta, amnion, and chorion express defensins at the level of transcription. These findings suggest that a novel and previously unrecognized mechanism of protecting the fetus against infection may be present within these tissues.

Amnion↗

[Experimental comparison of two coxsackievirus B3 variants in murine myocardial cells].

There is lack of direct evidence whether the myocarditis can be induced by CVB3o. The two coxsackievirus B3 variants were used to infected murine myocardial cells. The results showed that: (1) In culture medium of murine myocardial cells infected with two variants, it did not show much differences in titers at 12 and 24 hours between CVB3o and CVB3m. (2) The two variants could all induce the death of myocardium, but with the elapse of time, the cell death rate of CVB3m infected cells was much higher than CVB3o. (3) CVB3o could not block the myocardial cells from infection by CVB3m. It is concluded that myocardial cells can be infected by CVB3o, but the degree of infection is lower than CVB3m.

Animals↗

Changes in water activity and some microbial groups during storage of pet feed.

The effect of exposure of different pet feed samples to the typical temperature and moisture conditions of many months of the year (9 degrees C and 80% RH) on water activity (aw), pH and growth of various microbial groups (mesophilic aerobic bacteria, fungi and yeasts) was studied. The storage conditions were found to scarcely influence the samples pH, with no significant changes relative to the initial values (the standard deviation was 0.04 and the coefficient of variation 0.85%). By effect of exposure to the temperature and moisture conditions tested, the initially stable feeds reached moisture contents close to 20% and aw values near those of equilibrium with the ambient relative humidity during storage. Microbial counts increased with increasing aw, with final means of 8.44, 9.16 and 8.71 log CFU/g for mesophilic aerobic bacteria, fungi and yeasts, respectively. The risk of mycotoxin production at these aw values is discussed. Careful control of moisture is recommended in order to preserve the quality of pet feed throughout its scheduled shelf life.

Animal Feed↗

Nongenomic regulation of protein kinase C isoforms by the vitamin D metabolites 1 alpha,25-(OH)2D3 and 24R,25-(OH)2D3.

Prior studies have shown that vitamin D regulation of protein kinase C activity (PKC) in the cell layer of chondrocyte cultures is cell maturation-dependent. In the present study, we examined the membrane distribution of PKC and whether 1 alpha,25-(OH)2D3 and 24R,25-(OH)2D3 can directly regulate enzyme activity in isolated plasma membranes and extracellular matrix vesicles. Matrix vesicle PKC was activated by bryostatin-1 and inhibited by a PKC-specific pseudosubstrate inhibitor peptide. Depletion of membrane PKC activity using isoform-specific anti-PKC antibodies suggested that PKC alpha is the major isoform in cell layer lysates as well as in plasma membranes isolated from both cell types; PKC zeta is the predominant form in matrix vesicles. This was confirmed in Western blots of immunoprecipitates as well as in studies using control peptides to block binding of the isoform specific antibody to the enzyme and using a PKC zeta-specific pseudosubstrate inhibitor peptide. The presence of PKC zeta in matrix vesicles was further verified by immunoelectron microscopy. Enzyme activity in the matrix vesicle was insensitive to exogenous lipid, whereas that in the plasma membrane required lipid for full activity. 1,25-(OH)2D3 and 24,25-(OH)2D3 inhibited matrix vesicle PKC, but stimulated plasma membrane PKC when added directly to the isolated membrane fractions. PKC activity in the matrix vesicle was calcium-independent, whereas that in the plasma membrane required calcium. Moreover, the vitamin D-sensitive PKC in matrix vesicles was not dependent on calcium, whereas the vitamin D-sensitive enzyme in plasma membranes was calcium-dependent. It is concluded that PKC isoforms are differentially distributed between matrix vesicles and plasma membranes and that enzyme activity is regulated in a membrane-specific manner. This suggests the existence of a nongenomic mechanism whereby the effects of 1,25-(OH)2D3 and 24,25-(OH)2D3 may be mediated via PKC. Further, PKC zeta may be important in nongenomic, autocrine signal transduction at sites distal from the cell.

24,25-Dihydroxyvitamin D 3↗

Sebaceous carcinoma of the vulva: a case report and review of the literature.

Although sebaceous glands are prominent on the vulva, sebaceous carcinomas of the vulva rarely occur. In fact, there have been only two cases of sebaceous carcinomas of the vulva reported in the literature. Eighty percent of vulvar cancers are squamous in origin with human papillomavirus (HPV) DNA detected in approximately 60% of these cancers. We present a third patient with sebaceous carcinoma of the vulva and the first to our knowledge that has been analyzed for HPV DNA. The case report and a review of the literature are presented.

Adenocarcinoma, Sebaceous↗